Kojima I
Fourth Dept. of Internal Medicine University of Tokyo School of Medicine.
Gan To Kagaku Ryoho. 1989 Mar;16(3 Pt 2):489-98.
Insulin-like growth factor-I and II (IGF-I and II) are potent progression factors. In BALB/c 3T3 cells, IGFs exert the progression activity when quiescent cells are pretreated with platelet-derived growth factor and epidermal growth factor. In this IGF-responsive state, which we designated primed competent state, IGF-I and II stimulate calcium influx. The IGF-stimulated calcium influx sustains for at least few hours and is dependent on extracellular calcium concentration. To stimulate calcium influx IGF activates calcium-permeable cation channel. This IGF-sensitive channel is voltage-independent and is not totally selective for calcium. When IGF-mediated calcium influx is inhibited by either reduction of extracellular calcium or by adding cobalt or tetramethrin, IGF-induced DNA synthesis is attenuated. In either case, stimulation of calcium influx rate correlates quite well with the increase in DNA synthesis. Moreover, when calcium influx is augmented pharmacologically in primed competent cells by using BAY K8644, DNA synthesis is increased. These results suggest that calcium influx is an intracellular message of the mitogenic action of IGF-I and II.
胰岛素样生长因子-I和II（IGF-I和II）是强大的促增殖因子。在BALB/c 3T3细胞中，当静止细胞用血小板衍生生长因子和表皮生长因子预处理时，IGF发挥促增殖活性。在这种我们称为预激发的感受态状态下，IGF-I和II刺激钙内流。IGF刺激的钙内流持续至少数小时，并依赖于细胞外钙浓度。为了刺激钙内流，IGF激活钙通透性阳离子通道。这种IGF敏感通道不依赖电压，对钙也不是完全选择性的。当通过降低细胞外钙或添加钴或氯菊酯抑制IGF介导的钙内流时，IGF诱导的DNA合成减弱。在这两种情况下，钙内流速率的刺激与DNA合成的增加密切相关。此外，当通过使用BAY K8644在预激发的感受态细胞中通过药理学方法增强钙内流时，DNA合成增加。这些结果表明钙内流是IGF-I和II促有丝分裂作用的一种细胞内信号。
